Supporting data for "Role of tumour associated neutrophils in metabolic dysfunction-associated hepatocellular carcinoma development"
This dataset accompanies the thesis submitted for PhD candidature by Teo Jia Ming Nickolas. The data is also available under the GEO accession GSE240840.
The thesis regards the role of tumour associated neutrophils in metabolic dysfunction-associated hepatocellular carcinoma development. Neutrophils accumulate in solid tumours and their abundance are often associated with poor prognosis. Emerging evidence reveals that tumour-associated neutrophils (TANs) are highly heterogeneous, comprising of both pro- and anti-tumour subsets. Hence, TANs can differentially influence tumour progression and therapy efficacy depending on their diversity within the tumour microenvironment (TME). However, the factors driving TAN diversity, the functions of specific TAN subsets, and the spread of their heterogeneity in different cancer contexts remain largely unknown. Metabolic dysfunction-associated steatohepatitis (MASH) is the fastest growing cause of hepatocellular carcinoma (HCC). Crucially, despite abundant T cell infiltration, this fatty liver etiology is notoriously resistant towards immune checkpoint blockade (ICB) therapy. This treatment deficit likely arises from immunosuppressive factors in the TME. As neutrophils are one of the most prominent immune populations in the HCC TME, their diversity likely play key roles in MASH-HCC pathogenesis and ICB resistance. This thesis investigates how these TANs affect MASH-HCC progression, and how the MASH TME in turn shapes TAN development and diversification. Overall, this thesis has outlined a novel mechanism by which TANs promoted immune evasion and tumour aggressiveness. It also highlighted the importance of understanding how cancer etiology impacts the immune response within the TME.
During this investigation, two major types of datasets were generated. Firstly, single cell RNA-sequencing was performed on NRAS/AKT HCC-bearing mice bone marrow, spleen, and tumours (with or without aLy6G depletion). One sample of each was submitted for sequencing, and the resulting data is uploaded as feature-barcode matrices. Secondly, bulk RNA-seq of various experiments was performed, including: Transcriptomic profile of sort-purified TANs; Co-culture of RIL-175 HCC cells with sort-purified TANs; and Bone marrow neutrophils after overnight reprograming. Each experiment is available as count matrices, with the number of replicates indicated within the count matrix.
